Production of acridine compounds



Patented Jan. 1 1935 PATENT. QFF'ICE V I ROD CTION or. AORIDINE COMPOUNDS T Frederick Krana liufi'alo, N. Y., assignor to National Aniline- Chemical- Company, Inc., New York;-N."., a c'orporation of New York p No Drawing; Application spte1iib-er i2;=1929,

, SeriaiNo. 392255 This invention'relates to an improved process forthe production of acridine-compounds from diortho-diamino-diarylmethane compounds and their derivatives. l 5 This application is impart a continuation of my copending application, Serial No. 11,366, filed February 24, 1925. v j V g It is well known that diortho-diamino-diaryl methane compounds of the general formula where R represents an aryl nucleus in which an amino group occupies an ortho' position relative to the methane carbon atom and which nucleus may contain substituents in other positions, and R1 represents a hydrogen atom or an alkyl or aryl group, upon being heated with acids in an autoclave at elevated temperatures (130-150 (3.), eliminate ammonia and yield acridine compounds or their corresponding dihydro derivatives.

It is also known that tetramino-diphenylmethane compounds substituted in the amino groups by al yffi :acridine compounds when heated with acid erareflux condenser. I have found that polyamino-diarylmethane com! ds which are free from amino groups which contain substituent's yield acridine compounds-fwhenc heated at atmospheric pressure under reflux-conditions, I have also found it desirable in the condensation of the N-unsubstituted poly-amino diarylmethane compounds to acridine's to exclude air in order to'obviate'the obtainment' of poor products and poor yields. This-may be attained by carrying out the process at boiling temperature under a reflux condenser.v Under these conditions condensation takes place in a non-oxidizing 40 atmosphere, or nearly so, since steam or watervapor pra'ctically replaces theair originally present in the reaction vessel.

An object of the'invention' is to provide a process for the manufacture of acridine compounds from N -non-substituted polyamino-diphenylmethane bodies commercially and economically withoutthe use ofanautoclave.

Another objectof-the invention is to provide a process for the manufacture of acridine compounds from polyamino-diphenylmethane bodies with exclusion of: air under refluxing conditions. Other objects of the invention willin partbe obvious and will in part appear hereinafter;

According to the present invention, the eliminationof ammonia and the production of acriaforesaid about ,72

I di ne. compounds, for their dihydro derivities from N -non-substituted polyamino diphenylmethane compounds, for example tetramino-diphenylmethane compounds of the following probable formula: i

. mN- N115 HzN NH:

Where thebenzene nuclei may or may not contain substituents, such as CH3, etc., and R1 represents a hydrogen atom, an alkyl, or an aryl group,

of soluble, inert salts, the amount of sulfuricacid employed being about 3' to 4.5, preferably about 3.5 to 4, mols'or molecular proportions to each mol or molecular proportion of the diarylmeth'ane compound, and the amount of water approximateiy 2.5 to 6 or more times, preferablyiifi to 5.5, times the weight of thesuiiuric acid. In the absence of soluble salts the reaction mixture should boil preferably .at about 102. to 105 0,,

in their presenceat about 102 to 108 C., depending on the amount of' suchsalts present. Such non-oxidizing salts as sodium sulfate, sodium "Chloride, etc., ma be" "employed. Equiva1ent quantities ofother inorganic acids, such as hydrochloric acid, and other strong non-oxidizing inorganic acids may be used in place of sulfuric acid. I w

The following specific example will further illustrate the invention, but it istoi, be understoodthat the invention is not limited thereto. The parts are byweight'n Example: To 50 parts (I 11101) of swimmer;

2,2,4,4-tetraminodiphenylmethane, are added about335 parts water and about 80 parts (about 3.5 to .4 111015) of 66 B'vsulfu'riC acidv and the mixture is-boiled with vigorous agitation under a reflux condenser at atmospheric pressure for hours, or until. the reaction is completed. f l I Y Upon heating the mixture to its boiling point (about 1'02 104 0;), the tetraminoditolyl- If, in this example, a lesser'amount of. waterv is used, the time required to complete-the reaction is prolonged. For example,- if 180 parts of water instead of 335 parts are used, then about 96 hours is required to complete the reaction. The amount of acid may be varied somewhat without efiecting the yields to any greatextent. But, as the amountof acid is decreased below about 65 parts (about ,3 mols), by-products are formed in greater amounts; and if it is increased above about 95 parts (about 4.5 mols), the yield of acridine yellow decreases. Thus, not only the amount of acid used, but also its strength (which is determined by the amount of water present) is important if good yields are to be obtained. For best results, theamount of acid should be about 3.5 to 4 mols per mol of .tetraminoditolylmethane and the strength of the acid should be such that the mixture, in the absence of soluble inorganic salts, boils at about 102 to 104 C. By carrying out the process at boiling temperature. and

under a reflux condenser, the condensation is performed in a nearly non-oxidizing atmosphere, since water-vapor will have replaced the air above the reaction mixture. Various amounts of sodium sulfate, or other soluble inert salts, may

be present or added'to the mixture, in which case the boiling point will be higher than when such salts are absent.

Theprocess' can be also carried out under atmospheric pressure without using a reflux conidenser by conducting it man inert atmosphere (i. e., non-oxidizing atmosphere, e. g., steam, carbon dioxide, nitrogen, etc.) and keeping the volume of the reaction-mixture practically constant by the addition of water during the operation to replace that which is removed or lost by evaporation.

In a similar manner, other N-non-substituted 'tetraminoarylmethane compounds maybe consense.

I claim: I I

1. In the process of making acridine compounds from polyamino-diphenylmethane compounds which are free from amino groups that contain substituents, the improvement which comprises heating one molecular proportion of a said diphenylmethane compound to boiling under 'at- -mospheric pressure with about 3.5 to 4'molecular proportions of a strong,-non-oxidizing inorganic heating one molecular proportion, ofga said diphenylmethane compound under refluxing conditions at atmospheric pressure with about 3.5

to 4 molecular proportions of a strong, non-oxidizing inorganic acid while maintaining a non- I oxidizing atmosphere, and maintaining such an "amount oi waterfin the reaction mixture that the; mixture boils at about 102 to 104 C.

3, In'the process of making acridine compounds from polyamino-diphenylmethane compounds which are free from amino groups that contain substituents, the improvement which comprises heating one molecular proportion of a said diphenylmethane compound under refluxing conditions at atmospheric pressure with about 3.5 to 4 molecular proportions of sulfuric acid in the presence of water, the amount of water being such that themixture-boils at about 102-104 C.

4. In the process of making acridine compounds from polyamino-diphenylmethane compounds which are free from amino groups that contain substituents, the improvement which comprises heating one molecular proportion of a said diphenylmethane compound to boiling under refluxing conditions at atmospheric pressure with about 3 to 4.5 molecular proportions of sulfuric acid in the presence of an amount of water and ofv a soluble, non-oxidizing inorganic salt such under reflux conditions at atmospheric *rnessure with about 3 to 4.5 molecular proportions of sulfuric acid in thepresence of water, the amount of water being about 3.5 to 5.5 times the weight of acidemployed.

'7. In the process of making acridine compounds, the improvement which comprises heating one molecular proportion of 5,5-dimethyl- 2,2,4,4'-tetraminodiphenylmethane to boiling under reflux conditions at atmospheric pressure with about 3 to. 4.5 molecular proportions of sulfuric acid in the presence ofv an amount of 'water and of a soluble, non-oxidizing inorganic salt such that the mixture boils at 102-108 C.

. '8. In the. process of making acridine compounds from polyamino-diphenylmethane compounds which .are free fromJamino groupsthat contain substituents, the; improvement which comprises heating a said diphenylmethane compound witha strong non-oxidizing inorganic acid, in the presence of waterto boiling under atmospheric pressure in a non-oxidizing atmosphere.'

9.In the process of: making acridine compounds. from polyamino-diphenylmethane, compounds which are free .from amino. groups that contain substituents, the improvement which comprises heating a said diphenylmethane compound with sulfuric acid in the presence of water to boiling under atmospheric pressure in a non-oxidizing atmosphere.

10. In the process of making acridine compounds, the improvement which comprises heating 5,5 dimethyl 2,2',4,4' tertaminodiphenylmethane with sulfuric acid in the presence of water to boiling under reflux conditions at atmospheric pressure in a non-oxidizing atmosphere.

11. In the process of making acridine yellow, the improvementwhich comprises heating one molecular proportion of 5,5-dimethyl-2,2,4,4- tetraminodiphenylmethane to boiling at ordinary atmospheric pressure with about 3.5 to 4 molecular proportions of sulfuric acid while maintaining a non-oxidizing atmosphere, and maintaining such an amount of water in the reaction mixture that the mixture boils at about 102 to 104 C.

12. The process according to claim 11 in which the mixture is bofled under refluxing conditions for a period of about '72 hours.

13. In the process of making acridine yellow, the improvement which comprises heating one molecular proportion of 5,5'-dimethyl-2,2,4,4- tetraminodiphenylmethane to boiling under a reflux condenser under ordinary atmospheric pressure with about 3.5 to 4 molecular proportions of a strong non-oxidizing inorganic acid in the presence of water, the amount of water being such that the mixture boils at about 102 to 104 C.

14. The process according to claim 13 in which the mixture is boiled under a reflux condenser for a period of about 72 hours.

15. In the production of acridine yellow, a process which comprises heating one molecular proportion of 5,5-dimethyl-2,2,4,4-tetraminodiphenylmethane to boiling under atmospheric pressure with about 3 to 4.5 molecular proportions of sulfuric acid in the presence of an amount of water and of sodium sulfate such that the mixture boils at about 102-108 C.

16. In the process of making acridine yellow, the improvement which comprises heating one molecular proportion of 5,5-dimethy1-2,2',4,4'- tetraminodiphenylmethane to boiling under ordinary atmospheric pressure with about 3.5 to 4 molecular proportions of sulfuric acid in the presence of water, the amount of water being such that the mixture boils at about 102 to 104 C. I

17. The process according to claim 16 in which the mixture is boiled for a period of about 72 hours.

18. In the process of making acridine compounds from polyamino-diarylmethane compounds of the benzene series which are free from amino groups that contain substituents, the improvement which comprises heating one molecular proportion of a said amino-diarylmethan'e compound to boiling under atmospheric pressure with about 3 to 4.5 molecular proportions of a strong non-oxidizing inorganic acid in the pres ence of water, the amount of water being such that the mixture boils at about 102 to 105 C.

19. In the process of making acridine compounds from tetraminodiphenylmethane compounds which are free from amino groups which contain substituents, and which contain in each benzene nucleus an aminogroup in ortho position to the position linked to the methane carbon atom, the improvement which comprises heat ing one molecular proportion of said tetraminodiphenylmethane compound with 3 to 4.5 molecular proportions of sulfuric acid to boiling under atmospheric pressure in the presence of an amount of water such that the mixture is maintained at a boiling temperature of about 102 to 105? C. until the reaction is completed.

20. In the process of making acridine compounds from -diortho-diaminodiphenylmethane compounds which are free from amino groups which contain substituents, the improvement which comprises heating one molecular proportion of a said diortho-diaminodiphenylmethane compound to boiling under atmospheric pressure with about 3.5 to 4 molecular proportions of a strong non-oxidizing inorganic acid in the presence of water, the amount of water being such that the mixture boils at about 102 to 104 C.

- FREDERICK H. KRANZ.

Patent N0.'1,986,111.

' Certificate tr Corretion I I s January 1, 1935. FREDERICK KRANZ' It is hereby certified that errog's' appear in the printed specifieation of the abeve numbered patent requiring correctlonas follows: Page '1,' second column, line 1, for the words .for their dihydro derlvities read 'or their dihydrb'derivatives; and page 2,

first column, line 11,- at the extreme lower right portion of theform ula for CH read CH and that the said Letters Patent should be read wlth these corrections therethat the same may coiiform to the record of the case in the Patent Office.-

' Signed and sealed this 5th day ofFebruary, A. D. 1935. v

i LESLIE" FRAZER,

v {sen} Acting Commissioner of Patents. 

